chr5-55231740-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021147.5(CCNO):c.688G>A(p.Ala230Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000762 in 1,574,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
CCNO
NM_021147.5 missense
NM_021147.5 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 5.88
Genes affected
CCNO (HGNC:18576): (cyclin O) This gene encodes a member of the cyclin protein family, and the encoded protein is involved in regulation of the cell cycle. Disruption of this gene is associated with primary ciliary dyskinesia-19. Alternative splicing results in multiple transcript variants. This gene, which has a previous symbol of UNG2, was erroneously identified as a uracil DNA glycosylase in PubMed ID: 2001396. A later publication, PubMed ID: 8419333, identified this gene's product as a cyclin protein family member. The UNG2 symbol is also used as a specific protein isoform name for the UNG gene (GeneID 7374), so confusion exists in the scientific literature and in some databases for these two genes. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCNO | NM_021147.5 | c.688G>A | p.Ala230Thr | missense_variant | 3/3 | ENST00000282572.5 | |
CCNO | NR_125346.2 | n.1149G>A | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125347.2 | n.778G>A | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125348.1 | n.752G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCNO | ENST00000282572.5 | c.688G>A | p.Ala230Thr | missense_variant | 3/3 | 1 | NM_021147.5 | P1 | |
CCNO | ENST00000501463.2 | c.*668G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152272Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000108 AC: 2AN: 184512Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 98940
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GnomAD4 exome AF: 0.00000351 AC: 5AN: 1422534Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2AN XY: 703910
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GnomAD4 genome AF: 0.0000459 AC: 7AN: 152390Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74524
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.688G>A (p.A230T) alteration is located in exon 3 (coding exon 3) of the CCNO gene. This alteration results from a G to A substitution at nucleotide position 688, causing the alanine (A) at amino acid position 230 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2022 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 411601). This variant has not been reported in the literature in individuals affected with CCNO-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 230 of the CCNO protein (p.Ala230Thr). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.2674);
MVP
MPC
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at